Quinone compounds for treating Ape1 mediated diseases
The invention described herein pertains to compounds and compositions for treating Ape1 mediated diseases. In particular, the invention described herein pertains to quinone compounds and pharmaceutical compositions containing them for treating mediated diseases.
1. A method for treating a disease responsive to Ape1 inhibition in a host animal, the method comprising administering to the host animal a composition comprising a therapeutically effective amount of a compound of the formula
or a pharmaceutically acceptable salt thereof, wherein:
R A represents a fused aryl ring that is optionally substituted;
R is hydrogen or halo, or alkyl, heteroalkyl, cycloalkyl, cycloheteroalkyl, alkoxy, heteroalkoxy cycloalkoxy, cycloheteroalkoxy, alkylthio, heteroalkylthio cycloalkylthio, or cycloheteroalkylthio, each of which is optionally substituted;
X is alkylene, alkenylene, or alkynylene, each of which is optionally substituted; and
Y is N(R 1 ) 2 , NHOR 2 , or NR 2 OR 2 , where each R 1 is independently selected from the group consisting of alkyl, heteroalkyl, cycloalkyl, and cycloheteroalkyl, each of which is optionally substituted, or both R 1 are taken together with the attached nitrogen to form an optionally substituted heterocycle; where each R 2 is independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, cycloalkyl, and cycloheteroalkyl, each of which is optionally substituted, and a prodrug group, or both R 2 are taken together with the attached nitrogen and oxygen to form an optionally substituted heterocycle.
2. The method of claim 1 , wherein R A represents optionally substituted benzo.
3. The method of claim 1 , wherein R is alkyl or heteroalkyl, each of which is optionally substituted.
4. The method of claim 1 , wherein R is optionally substituted alkyl.
5. The method of claim 1 , wherein R is alkoxy.
6. The method of claim 1 , wherein R is alkylthio.
7. The method of claim 1 , wherein R is halo.
8. The method of claim 1 , wherein each R 1 is optionally substituted alkyl.
9. The method of claim 1 , wherein one R 1 is polyhydroxyalkyl.
10. The method of claim 1 , wherein both R 1 are taken together with the attached nitrogen to form an optionally substituted heterocycle selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, pyrrolidinone, piperidinone, piperazinone, and morpholinone.
11. The method of claim 1 , wherein at least one R 2 is hydrogen.
12. The method of claim 1 , wherein at least one R 2 is alkyl.
13. The method of claim 1 , wherein both R 2 are alkyl.
14. The method of claim 1 , wherein both R 2 are taken together with the attached nitrogen and oxygen to form an optionally substituted heterocycle selected from the group consisting of oxazolidine, oxazine, oxazapine, oxazolidinone, oxazinone, and oxazapinone.
15. The method of claim 1 , wherein X is optionally substituted alkylene.
16. The method of claim 1 , wherein X is optionally substituted alkenylene.
17. The method of claim 1 , wherein X is optionally substituted alkynylene.
18. The method of claim 1 , wherein the compound has the formula
or a pharmaceutically acceptable salt thereof.
19. The method of claim 1 , wherein the compound has the formula
or a pharmaceutically acceptable salt thereof.
20. The method of claim 1 , wherein the compound has the formula
or a pharmaceutically acceptable salt thereof.